Hypoxoside, (see below for structure), has been described in EPO Patent Application No. 83103765.0 and was obtained by the extraction of plants of the Hypoxidaceae family. In this patent application the applicant reported that hypoxoside has anticancer activity.
Extracts of plants of the Hypoxis genus (Hypoxidaceae) have been found to be active in tests against Mouse P388 lymphocytic leukemia cell cultures (A. Barclay and R. C. Perdue: Distribution of anticancer activity in higher plants. Cancer Treatment Reports, 1976, 60, 1081-1113 (I)). In addition, extracts of Hypoxis obtusa have been reported to have been used by certain African people for combating urinary diseases and the isolation of the acetylenic compound hypoxoside from this plant has been reported (G. B. Marini Bettolo, M. Patamia, M. Nicoletti, C. Galeffi and L. Messana: Tetrahedron, 1982, 38, 1683-1687 (II).
Acetylenic compounds occur widely in nature. Because of their antifungal, bacteriostatic and herbicidal properities as well as their potential application in medicine as hypnotic, sedative, anticonvulsant, analgesic anti-inflammatory and hypotensive agents considerable interest has been shown in the syntheses of these compounds. Numerous reviews cover the field of both natural and synthetic acetylenic compounds (the most comprehensive of these reviews are by K. E. Schulte and G. Rucker: Synthetische and naturliche Acetylen-Verbindungen als Arzneistoffe.--Progr. Drug Res 1970, 14, 387-563 (III) and by O. G. Yashina and L. I. Vereshchagin: Natural and Synthetic Acetylenic Antimycotics.--Russian Chem. Revs. (Transl.) 1978, 47, 307-317 (IV). Some acetylenic substances, although not structurally related to the compounds of the invention, have been found to be cytostatic and some have been used in the treatment of cancer (ref III). In addition some natural and synthetic acetylenoids have the pent-4-en-1-yne central unit.
Although these particular compounds possess some of the above mentioned biological properties none of them has been reported to be cytostatic nor have they been described as potential or actual anticancer agents (refs III and IV). Compounds of this invention that have been previously synthesized are compound 3 (J. Klein and S. Brenner: J.S.C.S., 1969, 91, 3094-3096 (V) and by V. Grignard: Bull. Soc. Chim. Fr., 1928, 43, 141-142, Compound 2 (ref. V) and Compounds 16 and 25 (ref. IV), but the quoted patent (DE No. 2025755-GB No. 1284475-U.S. Pat. No. 3,794,689. Chem Abstr., 1971, 74, 53260) describes different though closely related, substances: (HC.tbd.C).sub.2 C(OH).Ar.
It is the object of the present invention to prepare rooperol and describe its properties together with the preparation and properties of othe related compounds and derivatives; and secondly to describe the use of these compounds as anticancer agents.